1. Field of the Invention
The present invention is related to the medical field of hematology and, more particularly, for an improved method and device for the removal of disinfectant dyes such as methylene blue from blood, blood fractions or other perishable liquids to which the dyes have been added for disinfecting purposes.
2. Description of Related Art
At the present time one has only to mention human blood and blood transfusion to elicit anxiety related to fear of somehow contracting AIDS (Acquired Immunodeficiency Syndrome) from tainted blood. While it is true that various antibody-based and other tests have made it possible to remove the vast majority of HIV (Human Immunodeficiency Virus, the causative agent of AIDS) infected blood from our blood supply, the current status of AIDS as an incurable fatal disease makes even a relatively small risk unacceptable to many.
The risk of infection can be further reduced both by improving the sensitivity of diagnostic tests applied to the blood and by developing methods to disinfect the blood so that infected blood that evades the tests can be rendered substantially harmless. An additional advantage to the option of disinfecting blood is that there are many other blood-borne viral diseases besides AIDS. The public is generally aware of the several types of hepatitis that may be contracted from blood transfusions. These diseases range from being merely debilitating to being fatal as in the case of fulminating hepatitis or liver cancer, which is strongly correlated with certain forms of hepatitis. There are undoubtedly many other blood-borne viral pathogens that are as yet undiscovered.
One means of eliminating or removing viruses from blood is the use of "phototherapy" or "photodisinfection." Virtually all pathogenic agents, with the possible exception of "prions," are known to contain nucleic acids as their genetic material. Whereas nucleic acids in human cells are packaged by proteins and protected by the cytoplasm and the nuclear envelope, in typical viruses they are more exposed. This makes it possible to more readily cause photochemical damage to them. Nucleic acids naturally absorb light energy in the ultraviolet range. In fact, much of the skin damage caused by sunlight is due to photochemical damage to nucleic acids.
There have been some experiments with using ultraviolet light to disinfect blood, but this has generally not proven satisfactory. Levels of ultraviolet radiation that inactivate blood-borne pathogens are difficult to administer and may also cause damage to cellular and protein components of the blood. Furthermore, ultraviolet radiation can be difficult to work with and may damage or fail to penetrate materials commonly used in blood handling.
It is well-known that a chromophore absorbing light in the normal visible spectrum can be used to indirectly effect disinfection. Essentially, the chromophore absorbs visible light and becomes "excited." This extra energy from absorbing the light has to go somewhere: it can be converted into heat in the form of accelerated molecular vibration of the chromophore; it can be reemitted as fluorescence; or it can be used up in a photochemical reaction. Certain chromophores such as the thionine dye methylene blue (3,7-bis(dimethylamino)-phenazthionium chloride), when excited, is able to potentiate chemical reactions in nucleic acid. These photochemical reactions alter the structure of the nucleic acid and render it nonfunctional. Since living cells generally exclude the methylene blue, it is viral nucleic acids that are primarily liable to damage.
Although methylene blue is generally considered to be nontoxic, there is some trepidation at adding this material to blood and blood products for medical use. It is possible to remove methylene blue with binding substances such as activated charcoal. Unfortunately, many other substances stick to charcoal and are removed, thereby altering clinical chemistry and other diagnostic tests and potentially harming the quality of the transfused blood or blood product.
In addition, methylene blue and a number of other dyes are known to have "disinfectant" properties. This means that even in the absence of light these dyes may inhibit the growth of various microbes, especially bacteria. The cause of this disinfectant property is not entirely known. Since many of the disinfectant dyes have oxidation-reduction (redox) potentials in the range of many electron transport components of oxidative metabolism, it seems possible that these dyes operate by "short circuiting" these electron transport pathways. Generally the dyes show differential activity towards gram-negative versus gram-positive bacteria with electronegative dyes being more effective on gram-negative bacteria and electropositive dyes being more effective on gram-positive bacteria.
Human blood and blood fractions frequently have a limited shelf life because bacteria accidentally introduced into the blood from the skin of the blood donor multiply in the blood and eventually render it unusable. Until now no effective way of dealing with these bacterial contaminants has been developed. Addition of antibiotics or chemical disinfectants, while effective, is undesirable because of the problem of introducing these agents into the patient along with the blood or blood fraction.